Significance Measles is a highly infectious paramyxovirus that can cause an epizootic with almost 100% morbidity and up to 27% mortality in rhesus macaques. Due to the cost prohibitive nature of measles vaccination, many primate facilities elect not to immunize their colonies. Objective To determine if the canine distemper-measles vaccine was as effective as the currently used, but cost-prohibitive, measles vaccine in protecting rhesus macaques. Results The comparative measles vaccine trial (N=56) consisted of three vaccination regimens canine distemper-measles vaccine (CD-M), CD-M with a booster at 3 months post-immunization (CD-M+) and measles vaccine. Antibody titers were assessed via IFA at 0, 3, 7, and 11 months post-immunization. 100% of both CD-M vaccination groups developed detectable measles antibodies, while only 81.2% of the measles vaccination group developed detectable antibodies. One year post-vaccination, a subset of six juveniles from each vaccination group and three unvaccinated controls were challenged with measles virus. Virus isolation, serum-virus neutralization tests, naso-pharyngeal aspiration, CBC and FACS analysis were employed to assess viremia, neutralization antibodies, viral shedding and immune response respectively. Of the challenged juveniles, only the control animals developed the hallmark maculopapular rash. The control animals were found to be viremic for 21 days post-inoculation by observation of measles CPE in virus isolation and confirmed by measles IFA. Three measles vaccinated juveniles and two CD-M animals were confirmed viremic post-inocculation. Only the control animals shed measles virus when challenged; the viral shedding occurred during viremia and coincided with the appearance of the rash. Both CD-M vaccination groups had higher neutralization antibody titers and the CD-M+ vaccination group showed a greater than two fold increase in serum neutralization antibody titers over the measles vaccination group. Peripheral blood lymphocyte sub-populations in all groups were within normal reference ranges. Future Directions Determine protective measles antibody titers in rhesus macaques. KEYWORDS measles virus, rubeola, rhesus macaques, Macaca mulatta, clinical measles vaccine trial